FKBP8 (FKBP prolyl isomerase 8) is a constitutively inactive peptidyl-prolyl isomerase that becomes active when bound to calmodulin and calcium. The protein functions as a mitochondrial cargo receptor in selective autophagy (mitophagy), targeting damaged or excess mitochondria for degradation 12. FKBP8 serves as a crucial tethering protein at endoplasmic reticulum-mitochondria contact sites (MERCS), where it partners with the ER protein PDZD8 to regulate mitochondrial morphology and complexity 3. The protein acts as a chaperone for BCL2, targeting it to mitochondria and modulating its phosphorylation state, thereby playing a role in apoptosis regulation. FKBP8 is implicated in various disease contexts, including osteoarthritis where it represents a hub mitochondrial gene 4, and infectious diseases where pathogens like Mycobacterium bovis exploit host mitophagy pathways involving FKBP8 5. Clinically, FKBP8 degradation via RNF25-mediated ubiquitination promotes colorectal cancer liver metastasis by releasing mTOR signaling inhibition 6. Additionally, FKBP8 interaction with MLCK1 regulates intestinal barrier function, with therapeutic targeting showing promise for managing immune checkpoint inhibitor-induced colitis while preserving antitumor immunity 7.